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NIH Research Festival

September 23 – 25, 2024

Investigating the impact of non-myeloablative hematopoietic cell transplantation on organ pathology in the murine model of Sickle cell disease

Authors

  • A Idowu
  • D Gaskin
  • M Ali
  • D Kabore
  • X Xu
  • E Limerick
  • Z Quezado
  • D Springer
  • C Fitzhugh

Abstract

Sickle cell disease (SCD), a genetic disorder caused by a mutation in the β globin chain, leads to organ damage associated with early mortality. Hematopoietic cell transplantation (HCT) is the only curative therapy, but it is generally available to younger patients due to the toxicity of the conditioning regimen. We use a non-myeloablative approach to reduce the toxicity of the conditioning. However, little data exist about the impact of non-myeloablative HCT on brain, heart, and kidney damage in patients with SCD. Therefore, this project investigates the effects of non-myeloablative HCT on subsequent organ function. The transplant regimen included sirolimus and low-dose total body irradiation using the Townes SCD mouse model. Our results demonstrate that non-myeloablative HCT yields an average donor myeloid chimerism of 15 ±1.67% by 6 months post-HCT (endpoint). We also observed a significant reduction in the average sickle hemoglobin and an improvement in total hemoglobin levels post-HCT. Furthermore, our phenotype testing, which assessed neurocognitive behavior, showed that transplanted mice had improved Y-maze average percent alternation to that of the HbAA control mice by the endpoint. Additionally, echocardiograms showed a significant decrease in left ventricular systolic and diastolic volumes between transplanted mice versus HbSS control mice. Lastly, renal Doppler studies showed higher arterial resistance parameters (resistivity and pulsatility indexes) in the HbSS control mice versus the transplanted group. In addition to our ongoing studies, these results reveal that Townes mice successfully achieved mixed donor/recipient chimerism and showed improvement or stabilization in neurocognitive, cardiac, and renal function post-HCT.

Scientific Focus Area: Cell Biology

This page was last updated on Tuesday, August 6, 2024

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Current Research Festival

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    • General Schedule of Events
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